Inhibition of fatty acid oxidation enables heart regeneration in adult mice

Almost for any study that says X, you will find another one that says exactly the inverse.

It probably matters immensely which specific molecule is blocked and if you block one too early in some process then critical intermediates can’t be made. Sort of like deleting some code, it matters what’s downstream, so maybe earlier parts of this process are bad to block, but if you have a heart attack, then blocking later parts of the same process could trick your heart cells back into regenerating instead of being stable.

Also worth noting, this could be an example of hormesis. A metabolic approach to de-differentiate heart cells into a more primitive form by disrupting the way they process fats could be considered a toxic insult which triggers some defense (stemness) which is the proximate cause / helpful thing (not the toxic insult)

Does that contradict what is being said here, though? The straightforward reconciliation of the two: Some inhibition leads to regeneration; extended inhibition leads to runaway growth leading to abnormally enlarged cardiomusculature and health complications?

(I haven’t yet clicked your link, though!)

The study you linked shows that fatty acid oxidation accelerates cardiac hypertrophy.

The study linked above shows that fatty acid oxidation results in apparent hyperplastic and hypertrophic growth of the myocardium.

There are some significant differences between the observations in both studies, though, so they're not directly comparable. I wouldn't say they contradict each other though.

The two studies also reduced fatty acid oxidation very differently: One via microbiome manipulation and the other via genetic manipulation. Both routes will have side effects well beyond this singular measure, so they can't be compared directly.

Regardless, neither study is meant to indicate a viable medical procedure. The researchers are teasing out mechanisms that might be harnessed in the future to do something more useful.

Genetics matter a lot here for sure, mainly in that the genetics of mice vary greatly from all humans. It's still important to study and understand these interactions.

>>> You know what else inhibits fatty acid oxidation? CPT1A (Carnitine palmitoyltransferase I) Deficiency.

If I am not mistaken, the problem with CPT1A is upstream, way before oxidation occurs, in the breakdown of the long chain fatty acids before they can go into the mitochondria for oxidation. Unrelated to inhibiting oxidation

> you all are thick and dull because you never think genetics matter

This is uncalled for and untrue. There are a lot of human nutrition studies which account for genetics. It sounds like you’re angry, you should think about why that is before lashing out.

>In mice, they all have the same genetics, but as humans we vary more than you think.

This is deliberate, so that the research question can be isolated from variation in mouse genetics as much as possible. Different types of research use different mouse lineages according to their purposes. Do you think scientists are not aware of the role of genetics, or the great variability? The goal is to elucidate fundamental aspects of cell function:

>We conclude that metabolic maturation shapes the epigenetic landscape of cardiomyocytes

No one is trying to make you take a pill or alter your lifestyle because of this research.

If this study applies to you, here's a life advice: avoid cats.

Look up Dr Caldwell Esselstyn. He’s a doctor at the Cleveland Clinic who has consistently used diet to reverse his patients’ heart disease. It’s a low fat, low salt plant based diet. Dr McDougall is another. They both have a number of papers on the subject.

Edit: I’m not sure if McDougall’s papers are specifically on heart disease, actually, and can’t look it up conveniently at the moment. But he’s covered the topic in great depth.

Simply, unprocessed food and drinking plain water (not pure as in distilled but with sufficient electrolytes in it).

But the greatest impact would be lifestyle changes in general. You cannot just diet your way out of a heart disease.

Well, maybe this population [0] of subsistence farmers will give you a hint.

In the modern world it is an uphill battle. And there are some people with hypocholesterolemia [1] who will have arteries in near pristine condition despite living a modern (unhealthy) lifestyle.

There are two broad strategies here which can be combined:

(1) Adhering to (strict) rules which will consume your resource of willpower. A very effective one: Don't drink sugary drinks. An unconvenient one for most people: Don't eat out.

(2) Modifying your modern environment to such an extent that it resemble choices humans made before the modern lifestyle i.e. a lot of physical activity, offline times, no processed food, being outdoors (e.g. a garden). To reap the benefits from both a modern lifestyle and a lifestyle we are evolutionary adapted to, this of course will cost you money in a crowded city and (unpaid) time you would otherwise use for earning money.

[0]https://www.thelancet.com/journals/lancet/article/PIIS0140-6...

[1]https://www.sciencedirect.com/science/article/abs/pii/B97803...

The answer you are looking for is no. No one can translate this into what humans should eat to avoid heart disease, that will require a ton more research. We still haven't even figured out whether eggs are good or bad for you.

Vegetables and fruits. Less meat, especially red meat. Less fat. Especially reduce saturated fat. No refined sugar. Reduce salt. And: Exercise. Cardio sport . Increase muscle mass. And reduce stress. But most important: go to the cardiologist, take your meds, adhere to their advice.

My understanding is that exercise (of lack of) is significantly more important than diet.

I think a good summary of the things that most people agree on to some extent is Michael Pollan's advice from The Omnivore's Dilemma (2006): "Eat food. Not too much. Mostly plants."

Obviously there are a lot of details to fill in, but the first part boils down to avoiding processed foods. The other two are pretty straightforward.

As mentioned by others, physical activity and stress management are just as important, and social connections tend to be positively correlated with health as well.

I think the problems come in when you realize how many people pushing specific diets have agendas beyond health, as well as the fact that there is no specific diet that is perfect for everyone.

Whole food vegan diet. My cholesterol went down 20 points in a bit more than a year. Bracing for the oncoming cholesterol apologists... My doctor says that vegan diets are unequivocally better for the heart according to the literature.

The best thing to do is go on walks. Walking and getting your heart rate up to 120-ish not only is shown to help slow or stop the progression of Aatherosclerosis, it also helps prevent clots from forming in your legs and causing serious issues elsewhere. The only other advice is to avoid excess in your diet.

it's less about what foods to eat and more about eating much less: one modest-sized meal a day. that's all we "need". we eat too much of everything and our bodies are not evolved for such excess. this is literally the biggest bang for buck for chronic diseases like this, but also the hardest thing to do because of socio-cultural considerations. it also takes some time to train your digestive system down to that level.

once you have amounts under control, then you can taper off the processed foods, especially sugary things like soda/juice (fruit is ok because it comes with fiber), salty things like chips/frozen dinners, and bread/rice products (a little whole grain here and there is ok). minimize processed foods but don't worry too much about the mix of foods otherwise (protein/fat is fine, just don't overeat).

then taper up anaerobic exercise to 2-3 times a week. find a sport or activity you like (e.g., tennis) and pay for an organized league/class so that you stay committed. (aerobic) walking, for instance, is not typically strenuous enough for your body to process the excess nutrients and improve cardiovascular fitness, which is what's needed to help keep heart disease under control. you can start with walking if you're in bad shape, but you'll want to graduate to anaerobic exercise as soon as you can.

By decreasing your chances to die from heart attack fast and without much pain, you are increasing your chances of long and painful death from cancer..

How are their hearts?

What does "pe." mean in this context?

(fatty acid oxidation inhibitor)

Agreed on the common sense stuff but disagree about the difficulty to translate this to practice. Depends if you need it from Big Pharma or if you’re biohacking.

The authors highlight a multi step pathway and one of the steps is accumulation of alpha-ketoglutarate which is a common ketone we all already have tons of, and it increases from fasting. Seems like their research indicates there’s a second system hiding behind the first and it only turns on when you have ketones and can’t burn fat. That’s like the logical converse or contrapositive or something to fasted state. This is analogous to diabetic ketoacidosis but seems to have a healthy impact, which is surprising.

TLDR: if you think about it, fatty acid oxidation pathways are some of the easiest to target (even with zero drugs…just stop eating for a few days)

Really 99.9%?

The thing is that even if this is is true we can explore things like TOR which mice definitely have and it definitely adds to the list of evidence that inhibiting TOR extends lifespan

The problem isn't that the drug results don't translate from mice to humans. The problem is that after testing the drug successfully in mice, they follow that with testing the marketing campaign with the mice. The mice never buy the drug, so they decide to drop it as unprofitable and move on to another drug.

Seems to me if mice ever develop advanced intelligence they will either hate us for the experiments or be grateful to have the medical knowldge to extend their lifespans and cure every one of their disease under the sun. Maybe both?

This wasn’t heart regeneration in ordinary mice, though - it was in genetically modified mice.

So if you want your heart to regenerate using this technology, you need to go back in time and edit your genes before you were born.

It shows it’s biologically possible for mammalian cardiac cells to (a) do the job of the heart while (b) being regenerated. That’s not clinically relevant for humans. But it’s scientifically relevant for researchers (and those interested in the science of it).

There must be some SF out there where immortal and invincible mice escape the lab and soon we have a paper clip maximizer like situation. The Mice Maximizer?

Some are worried about AGI, should we be more concerned about super mice ?

TIL Mighty Mouse was a sci-fi cartoon

Please refer to Douglas Adams Hitchhiker’s Guide to the Galaxy for the real story about humanity, the earth and the mice. We’re just components in a machine to answer questions for the mice.

Don't forget the Cats

Yes eventually we may get them to living 15+ years.

Mice have a lot of room for improvement. I'll be impressed when we figure out how to double the lifespan of sea turtles.

Why?

You are the one that's confused if your conclusion is fat = bad for the heart based on this.

Oxidizability varies between types of fat. Saturated fat (as the name suggests) doesn’t react as easily. The microbiome (ideally) produces butyrate and other short chained fatty acids, which are required for healthy metabolism. Those also don’t oxidize as easily.

Why was this person downvoted? High-fat diets absolutely increase fatty acid oxidation; it's literally one of their (deceptive) selling points.